Sucrose is generally regarded as the main dietary cause of dental caries. However, considerable consternation in both the scientific literature and the popular press has been directed at the safety of saccharin and aspartame, the only presently approved sucrose substitutes in the United States. The plant kingdom has already afforded a number of intense sweeteners of commercial significance, including glycyrrhizin, thaumatin, stevioside, and phyllodulcin, and holds the potential for the discovery of additional potentially noncariogenic and noncaloric sucrose substitutes. In recent years, however, there has been increasing concern over the need to use human subjects to assess the sweetness of compounds, of either natural or synthetic origin, that have not been subjected to prior toxicity studies. It is proposed in this investigation to evaluate 16 structurally diverse sweet compounds of natural origin in electrophysiological and behavioral taste experiments utilizing the Mongolian gerbil (Meriones unguiculatus). Further, it is intended to assess the feasibility of using the gerbil to fractionate additional plant-derived sweeteners from Stevia rebaudiana and Thladiantha grosvenori, and to guide the chromatographic isolation of the previously incompletely characterized sweet constituent(s) of the tropical plant, Abrus precatorius. The data obtained on the characterization of additional sweet compounds will add to knowledge on the structural requirements for sweetness among the diterpene glycoside and triterpene glycoside classes of plant-derived intense sweetners. This investigation should indicate whether the Mongolian gerbil may have more general utility for the preliminary evaluation for sweetness of naturally occurring and synthetic chemical entities, and could therefore reduce or eliminate the need for human involvement at this stage, and the necessity for expensive supporting toxicological studies to determine whether such compounds are safe for humans to taste.